The applicability of molecular descriptors for designing an electrospray ionization mass spectrometry compatible library for drug discovery

Jennifer C. Copeland, Levi J. Zehr, Ronald Cerny, Robert Powers

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Detecting a small molecular-weight compound by electrospray ionization mass spectrometry (ESI-MS) requires the compound to obtain a charge. Factors such as gas-phase proton affinities and analyte surface activity are correlated with a positive ESI-MS response, but unfortunately it is extremely challenging to predict from a chemical structure alone if a compound is likely to yield an observable molecular-ion peak in an ESI-MS spectrum. Thus, the design of a chemical library for an ESI-MS ligand-affinity screen is particularly daunting. Only 56.9% of the compounds from our FAST-NMR functional library [1] were detectable by ESI-MS. An analysis of ∼1,600 molecular descriptors did not identify any correlation with a positive ESI-MS response that cannot be attributed to a skewed population distribution. Unfortunately, our results suggest that molecular descriptors are not a valuable approach for designing a chemical library for an MS-based ligand affinity screen.

Original languageEnglish (US)
Pages (from-to)806-815
Number of pages10
JournalCombinatorial Chemistry and High Throughput Screening
Volume15
Issue number10
StatePublished - Dec 1 2012

Fingerprint

Electrospray ionization
Electrospray Ionization Mass Spectrometry
Drug Discovery
Libraries
Mass spectrometry
Small Molecule Libraries
Ligands
Population distribution
Protons
Molecular Weight
Gases
Molecular weight
Nuclear magnetic resonance
Demography
Ions

Keywords

  • Chemical library
  • Drug discovery
  • Electrospray ionization
  • Ligand-affinity screens
  • Mass spectrometer
  • Molecular descriptors

ASJC Scopus subject areas

  • Drug Discovery
  • Computer Science Applications
  • Organic Chemistry

Cite this

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abstract = "Detecting a small molecular-weight compound by electrospray ionization mass spectrometry (ESI-MS) requires the compound to obtain a charge. Factors such as gas-phase proton affinities and analyte surface activity are correlated with a positive ESI-MS response, but unfortunately it is extremely challenging to predict from a chemical structure alone if a compound is likely to yield an observable molecular-ion peak in an ESI-MS spectrum. Thus, the design of a chemical library for an ESI-MS ligand-affinity screen is particularly daunting. Only 56.9{\%} of the compounds from our FAST-NMR functional library [1] were detectable by ESI-MS. An analysis of ∼1,600 molecular descriptors did not identify any correlation with a positive ESI-MS response that cannot be attributed to a skewed population distribution. Unfortunately, our results suggest that molecular descriptors are not a valuable approach for designing a chemical library for an MS-based ligand affinity screen.",
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AU - Zehr, Levi J.

AU - Cerny, Ronald

AU - Powers, Robert

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N2 - Detecting a small molecular-weight compound by electrospray ionization mass spectrometry (ESI-MS) requires the compound to obtain a charge. Factors such as gas-phase proton affinities and analyte surface activity are correlated with a positive ESI-MS response, but unfortunately it is extremely challenging to predict from a chemical structure alone if a compound is likely to yield an observable molecular-ion peak in an ESI-MS spectrum. Thus, the design of a chemical library for an ESI-MS ligand-affinity screen is particularly daunting. Only 56.9% of the compounds from our FAST-NMR functional library [1] were detectable by ESI-MS. An analysis of ∼1,600 molecular descriptors did not identify any correlation with a positive ESI-MS response that cannot be attributed to a skewed population distribution. Unfortunately, our results suggest that molecular descriptors are not a valuable approach for designing a chemical library for an MS-based ligand affinity screen.

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